1-(4-Fluorophenyl)piperazine → 1-Acetyl-3-[4-(4-fluorophenyl)piperazin-1-ylmethyl]-1H-indazole

HRID 1956367Notes

Reaction equation

HRID 1956367 reaction equation
[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:13]Br)=[N:5]1)(=[O:3])[CH3:2].[F:15][C:16]1[CH:21]=[CH:20][C:19]([N:22]2[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]2)=[CH:18][CH:17]=1.CCN(C(C)C)C(C)C.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[C:1]([N:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[C:6]([CH2:13][N:25]2[CH2:24][CH2:23][N:22]([C:19]3[CH:18]=[CH:17][C:16]([F:15])=[CH:21][CH:20]=3)[CH2:27][CH2:26]2)=[N:5]1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 752601-(4-Fluorophenyl)piperazineHCID 81531DiisopropylethylamineHCID 516892Sodium BicarbonateHCID 137502691-(3-(Bromomethyl)-1H-indazol-1-yl)ethanone

Product 1

HCID 186632371-Acetyl-3-[4-(4-fluorophenyl)piperazin-1-ylmethyl]-1H-indazole

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
20 °C

Procedure

1-Acetyl-3-bromomethyl-1H-indazole (160 mg, 0.63 mmol) in CH2Cl2 (5 mL) was treated with 1-(4-fluorophenyl)piperazine (228 mg, 1.26 mmol) and Hunig's base (102 mg, 0.79 mmol) and the mixture stirred at 20° C. for 16 h. The mixture was poured into saturated aqueous sodium bicarbonate solution (10 mL) and extracted with CH2Cl2 (3×10 mL). The combined organic extracts were dried (MgSO4), concentrated and the residue purified by flash chromatography (10%→25% EtOAc in hexane) to give the title compound as a white solid. This was recrystallised from ether/hexane to give colourless crystals (184 mg, 83%); mp 119°-120° C. (from ether/hexane); 1H NMR (360 MHz, d6 -DMSO) δ8.31 (d, J=8.3 Hz, 1 H, indazole), 8.08 (d, J=8.3 Hz, 1H, indazole), 7.63 (t, J=8.3 Hz, 1H, indazole), 7.43 (t, J=8.3 Hz, 1H, indazole), 7.03 (m, 2H, Ph), 6.93 (m, 2H, Ph), 3.95 (s, 2H, Ar--CH2N), 3.08 (m, 4H, piperazine), 2.70 (s, 3H, Ac), 2.64 (m, 4H, piperazine); MS (CI+) m/e 353 M+H+); Anal. calcd for C20H21N4OF: C, 68.16; H, 6.01; N, 15.90. Found: C, 68.15;H, 5.85; N, 15.64.

Workup

  1. extractionextracted with CH2Cl2 (3×10 mL)
  2. dry with materialThe combined organic extracts were dried (MgSO4)
  3. concentrationconcentrated
  4. customthe residue purified by flash chromatography (10%→25% EtOAc in hexane)

Sources & evidence

ORD record
ord-4d3ead99ebe149e88347a6883b0eb5b6
Source dataset
uspto-grants-1998_07
Patent number
US05780475

Reaction notes

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